Medical Discovery News: Taking advantage of side effects

Biomedical science has developed many drugs to treat all manner of maladies. Most of these marvels of medicine are designed to alleviate the symptoms or root causes of a specific disease. In many cases, these powerful drugs have “side effects” in other areas of the body. Side effects are listed in fine print on medicine packaging and they are part of every television commercial marketing these drugs to people. Many scientists are realizing that side effects can be clues to treatment of other diseases.

The idea of re-purposing drugs as treatments for other diseases is an active avenue of investigation in today’s drug discovery and development efforts. Recently, experimentation has uncovered that a commonly used antibiotic called doxycycline may represent a new treatment for Parkinson’s disease. Low doses of this drug have been shown to work by reducing inflammation in the brain. Specifically, it reduces the toxicity of a protein called alpha-synuclein, which accumulates and aggregates inside nerve cells.

The classic symptoms of Parkinson’s disease are tremors, muscle stiffness and slow movement. While we do not know exactly why this occurs, it has been shown to involve alterations of nerve function. We know that a certain class of neurons are damaged and eventually killed during the progression of the disease. These neurons produce the neurotransmitter dopamine. Dopamine is the signal that allows nerve impulses to be spread in the body. The neurons are killed when alpha-synuclein accumulates.

Researchers discovered the protective role of doxycycline while treating mice with 6-OHDA, a chemical that kills these neurons in mice. Treatment with 6-OHDA is a reliable way to induce Parkinson’s disease in mice for study.

However, researchers noticed that suddenly the mice did not show symptoms of the Parkinson’s-like disease after 6-OHDA treatment. The mouse model is normally reliable, so the researchers knew something was going on. In a great example of scientific sleuthing, the researchers discovered that the animals’ food contained low levels of doxycycline. This led to a series of experiments exploring the possible protective effect of the antibiotic. Using nerve cells in culture, they showed that when low doses of doxycycline were included, the nerve cells did not die. Alpha-synuclein still aggregated but was reduced by up to 80 percent, and there was no resulting damage to the cells.

Doxycycline may affect other mechanisms of Parkinson’s disease also. Doxycycline leads to a reduction in the inflammatory conditions that likely contribute to the death of the nerve cells. This could be because of a reduction of key mediators of inflammation called cytokines. There is also some evidence that doxycycline may influence genes that directly play a role in Parkinson’s disease. While how this all works is not completely understood, the results are promising and point to a possible new use for an existing drug.

This is a great example of the re-purposing of a drug. Of course, the true value will have to be assessed by additional animal experimentation, followed by human clinical trials to assess whether Parkinson’s symptoms are reduced after treatment with doxycycline.

Medical Discovery News is hosted by professors Norbert Herzog at Quinnipiac University, and David Niesel of the University of Texas Medical Branch. Learn more at www.medicaldiscoverynews.com.